This international prospective study showed that maintenance therapy with rituximab was more effective than interferon alfa in prolonging the duration of remission and extending survival in older ...patients with mantle-cell lymphoma.
Patients with mantle-cell lymphoma typically present with extensive disease and involvement of multiple lymph nodes as well as the spleen, bone marrow, blood, and gastrointestinal tract. The median age at diagnosis is about 65 years.
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Standard therapy for these patients consists of chemotherapy (e.g., the CHOP regimen, consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone) combined with the anti-CD20 monoclonal antibody rituximab (e.g., R-CHOP).
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Only a minority of patients have a complete remission, and relapse or progression usually occurs within 2 to 3 years, resulting in an overall survival of less than 5 years.
To improve this grim prognosis, . . .
Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms.
This phase II study evaluated the response rate of copanlisib administered ...intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis.
Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2–138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0–874) and 70 days (range 0–897), respectively; median duration of response was 390 days (range 0–825) and 166 days (range 0–786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression.
Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing.
This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).
•This updated ESMO Clinical Practice Guideline provides key recommendations on the management of follicular lymphoma.•Authorship includes a multidisciplinary group of experts from different ...institutions and countries in Europe and abroad, including levels of evidence and grades of recommendation where applicable.•In localised stages, combination of radiation and rituximab monotherapy may be considered.•In advanced stages, either obinutuzumab or rituximab may be combined with chemotherapy.•In early relapses, a switch of chemotherapy and antibody is recommended. In younger patients, an autologous stem-cell transplantation should be discussed.•In older patients with either early, first or later relapses, lenalidomide in combination with rituximab may be considered.
Introduction: The Bruton tyrosine kinase (BTK) is a central hub in the B cell receptor (BCR) pathway and strongly influences B cell maturation, differentiation and proliferation. Not surprisingly, ...BTK plays an essential role in the pathogenesis of various B cell lymphomas. Inhibitors of BTK have broadened our therapeutic options in several B cell lymphomas and already are an integral element in the treatment of Mantle Cell Lymphoma (MCL), chronic lymphocytic leukemia (CLL) and Waldenström's marcoglobulinemia. Several second generation BTK inhibitors are in clinical development and might further improve tolerability and efficacy of therapy in advanced stage CLL and MCL.
Areas covered: This review illustrates the mechanism of action of BTK inhibitors and provides a comprehensive summary of key clinical trials in the development of BTK inhibitors. Characteristics of second generation BTK-inhibitors are described.
Expert opinion: With accumulation of clinical experience after drug approval, longer patient follow-up and larger numbers of treated patients, future development will focus on the identification of intelligent treatment combinations. Individual selection of patients with distinct biologically properties might guide treatment decisions. While BTK inhibitors are moving to earlier treatment lines, the incorporation of these drugs into a comprehensive therapeutic strategy is still difficult to date.
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